Use of Syncytin for Targeting Drug and Gene Delivery to Lung Tissue

Abstract

The invention relates to a pharmaceutical composition for targeting drug delivery including gene delivery to lung tissue, comprising at least a therapeutic drug or gene associated to a syncytin protein, and its use in the prevention and/or treatment of lung diseases, in particular in gene therapy of said diseases using lentiviral vector particles or lentivirus-like particles pseudotyped with syncytin protein.

1 - 15 . (canceled) 
     
     
         16 . A method of preventing and/or treating lung diseases in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition targeting lung tissue, comprising at least a therapeutic drug associated to a syncytin protein. 
     
     
         17 . The method according to  claim 16 , wherein the syncytin protein is human or murine syncytin. 
     
     
         18 . The method according to  claim 17 , wherein the syncytin is selected from the group consisting of human Syncytin-1, human Syncytin-2, murine syncytin-A and murine syncytin-B. 
     
     
         19 . The method according to  claim 16 , wherein the therapeutic drug and the syncytin protein are incorporated into particles. 
     
     
         20 . The method according to  claim 19 , wherein the particles are selected from the group consisting of liposomes, exosomes, viral particles and virus-like particles. 
     
     
         21 . The method according to  claim 19 , wherein the syncytin protein is displayed on the surface of the particles. 
     
     
         22 . The method according to  claim 19 , wherein the particles are lentiviral or lentiviral-like particles pseudotyped with syncytin protein. 
     
     
         23 . The method according to  claim 16 , wherein the drug is selected from the group consisting of therapeutic genes, genes encoding therapeutic proteins or peptides, therapeutic antibodies or antibody fragments, genome editing enzymes, interfering RNA, guide RNA for genome editing, antisense RNA capable of exon skipping; anti-bacterial drugs, anti-viral drugs, anti-fungal drugs, anti-parasitic drugs; anti-inflammatory drugs; immunotherapeutic drugs, immunomodulatory drugs, immunosuppressive drugs, anti-allergic drugs, anti-histaminic drugs and immunostimulating drugs. 
     
     
         24 . The method according to  claim 19 , wherein the drug is a gene of interest packaged into a viral vector particle. 
     
     
         25 . The method according to  claim 16 , wherein the drug is a gene of interest packaged into a lentiviral vector particle pseudotyped with syncytin protein. 
     
     
         26 . The method according to  claim 16 , wherein the lung diseases are selected from the group consisting of: genetic diseases affecting the lungs; infectious diseases affecting the lungs; inflammatory or auto-immune diseases of the lungs, asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, oedema, emphysema, hypertension, acute respiratory distress syndrome, pneumoconiosis, interstitial lung disease, diffuse parenchymal lung disease, lung transplant rejection and lung disease in new born and premature babies. 
     
     
         27 . The method according to  claim 16 , for use in gene therapy of the lung diseases. 
     
     
         28 . The method according to  claim 16 , wherein the drug is a gene of interest for therapy selected from the group consisting of: SERPINA3, SERPINA1, MMP, in particular MMP1, MMP2 and MMP9, CFTR, SFTPB, SFTPC, ABCA3, CSF2RA, TERT, TERC, SFTPA2, SLC34A2, DKC1, TERC, TERT, TINF2, NF1, TSC1, FLCN, STAT3, HPS1, GBA, SMPD1, SLC7A7, SMAD9, KCNK3 and CAV1 genes, and functional variants thereof. 
     
     
         29 . The method according to  claim 16 , which is for administration by injection, inhalation or broncho-alveolar lavage. 
     
     
         30 . A pharmaceutical composition targeting lung tissue, comprising virus particles pseudotyped with syncytin protein, packaging a gene of interest selected from the group comprising: the genes SERPINA3, SERPINA1, MMP, in particular MMP1, MMP2 and MMP9, CFTR, SFTPB, SFTPC, ABCA3, CSF2RA, TERT, TERC, SFTPA2, SLC34A2, DKC1, TERC, TERT, TINF2, NF1, TSC1, FLCN, STAT3, HPS1, GBA, SMPD1, SLC7A7, SMAD9, KCNK3, CAV1, functional variants thereof, interfering RNA, guide RNA for genome editing, antisense RNA capable of exon skipping, wherein the RNA target the gene of interest. 
     
     
         31 . The pharmaceutical composition according to  claim 30 , wherein the virus particles are lentiviral vector particles. 
     
     
         32 . A pharmaceutical composition for targeting lung tissue, comprising virus-like particles, pseudotyped with syncytin protein, an interfering RNA, guide RNA for genome editing or antisense RNA capable of exon skipping, said RNA targeting a gene of interest selected from the group of genes comprising: SERPINA3, SERPINA1, MMP, in particular MMP1, MMP2 and MMP9, CFTR, SFTPB, SFTPC, ABCA3, CSF2RA, TERT, TERC, SFTPA2, SLC34A2, DKC1, TERC, TERT, TINF2, NF1, TSC1, FLCN, STAT3, HPS1, GBA, SMPD1, SLC7A7, SMAD9, KCNK3 and CAV1. 
     
     
         33 . The pharmaceutical composition according to  claim 32 , wherein the virus-like particles are lentivirus-like particles.